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Because of the physiological role of cell death during development, aberration of normal apoptotic cell death is detrimental to normal organogenesis.<\/jats:p><jats:p>Apoptosis occurs in not only neuron but also in NPCs and neuroblast. When growth and survival signals such as EGF or LIF are removed, apoptosis is activated as well as the induction of differentiation. To investigate the regulation of cell death during developmental stage, it is essential to investigate the regulation of apoptosis of NPCs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Neural progenitor cells were cultured from E14 embryonic brains of Sprague-Dawley rats. For<jats:italic>in vivo<\/jats:italic>VPA animal model, pregnant rats were treated with VPA (400 mg\/kg S.C.) diluted with normal saline at E12. To analyze the cell death, we performed PI staining and PARP and caspase-3 cleavage assay. Expression level of proteins was investigated by Western blot and immunocytochemical assays. The level of mRNA expression was investigated by RT-PCR. Interaction of Bcl-XL gene promoter and NF-\u03baB p65 was investigated by ChIP assay.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In this study, FACS analysis, PI staining and PARP and caspase-3 cleavage assay showed that VPA protects cultured NPCs from cell death after growth factor withdrawal both in basal and staurosporine- or hydrogen peroxide-stimulated conditions. The protective effect of prenatally injected VPA was also observed in E16 embryonic brain. Treatment of VPA decreased the level of I\u03baB\u03b1 and increased the nuclear translocation of NF-\u03baB, which subsequently enhanced expression of anti-apoptotic protein Bcl-XL.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>To the best of our knowledge, this is the first report to indicate the reduced death of NPCs by VPA at developmentally critical periods through the degradation of I\u03baB\u03b1 and the activation of NF-\u03baB signaling. The reduced NPCs death might underlie the neurodevelopmental defects collectively called fetal valproate syndrome, which shows symptoms such as mental retardation and autism-like behavior.<\/jats:p><\/jats:sec>","DOI":"10.1186\/1423-0127-18-48","type":"journal-article","created":{"date-parts":[[2011,8,19]],"date-time":"2011-08-19T18:14:21Z","timestamp":1313777661000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Valproic acid inhibits neural progenitor cell death by activation of NF-\u03baB signaling pathway and up-regulation of Bcl-XL"],"prefix":"10.1186","volume":"18","author":[{"given":"Hyo Sang","family":"Go","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jung Eun","family":"Seo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ki Chan","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"So Min","family":"Han","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pitna","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young Sun","family":"Kang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seol Heui","family":"Han","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chan Young","family":"Shin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kwang Ho","family":"Ko","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2011,7,4]]},"reference":[{"key":"302_CR1","doi-asserted-by":"publisher","first-page":"1258","DOI":"10.1126\/science.6474175","volume":"225","author":"WM Cowan","year":"1984","unstructured":"Cowan WM, Fawcett JW, O'Leary DD, Stanfield BB: Regressive events in neurogenesis. 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